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Database: UniProt
Entry: O62725
LinkDB: O62725
Original site: O62725 
ID   PGH2_NEOVI              Reviewed;         604 AA.
AC   O62725;
DT   15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1998, sequence version 1.
DT   16-JAN-2019, entry version 119.
DE   RecName: Full=Prostaglandin G/H synthase 2;
DE            EC=1.14.99.1;
DE   AltName: Full=Cyclooxygenase-2;
DE            Short=COX-2;
DE   AltName: Full=PHS II;
DE   AltName: Full=Prostaglandin H2 synthase 2;
DE            Short=PGH synthase 2;
DE            Short=PGHS-2;
DE   AltName: Full=Prostaglandin-endoperoxide synthase 2;
DE   Flags: Precursor;
GN   Name=PTGS2; Synonyms=COX2;
OS   Neovison vison (American mink) (Mustela vison).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Laurasiatheria; Carnivora; Caniformia; Mustelidae;
OC   Mustelinae; Neovison.
OX   NCBI_TaxID=452646;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Uterus;
RX   PubMed=9681517; DOI=10.1210/endo.139.8.6142;
RA   Song J.H., Sirois J., Houde A., Murphy B.D.;
RT   "Cloning, developmental expression, and immunohistochemistry of
RT   cyclooxygenase 2 in the endometrium during embryo implantation and
RT   gestation in the mink (Mustela vison).";
RL   Endocrinology 139:3629-3636(1998).
CC   -!- FUNCTION: Converts arachidonate to prostaglandin H2 (PGH2), a
CC       committed step in prostanoid synthesis. Constitutively expressed
CC       in some tissues in physiological conditions, such as the
CC       endothelium, kidney and brain, and in pathological conditions,
CC       such as in cancer. PTGS2 is responsible for production of
CC       inflammatory prostaglandins. Up-regulation of PTGS2 is also
CC       associated with increased cell adhesion, phenotypic changes,
CC       resistance to apoptosis and tumor angiogenesis. In cancer cells,
CC       PTGS2 is a key step in the production of prostaglandin E2 (PGE2),
CC       which plays important roles in modulating motility, proliferation
CC       and resistance to apoptosis. {ECO:0000250|UniProtKB:Q05769}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + AH2 + 2 O2 = A + H2O
CC         + prostaglandin H2; Xref=Rhea:RHEA:23728, ChEBI:CHEBI:13193,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:17499,
CC         ChEBI:CHEBI:32395, ChEBI:CHEBI:57405; EC=1.14.99.1;
CC         Evidence={ECO:0000250|UniProtKB:Q05769};
CC   -!- COFACTOR:
CC       Name=heme b; Xref=ChEBI:CHEBI:60344;
CC         Evidence={ECO:0000250|UniProtKB:Q05769};
CC       Note=Binds 1 heme b (iron(II)-protoporphyrin IX) group per
CC       subunit. {ECO:0000250|UniProtKB:Q05769};
CC   -!- PATHWAY: Lipid metabolism; prostaglandin biosynthesis.
CC       {ECO:0000250|UniProtKB:P35354}.
CC   -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q05769}.
CC   -!- SUBCELLULAR LOCATION: Microsome membrane; Peripheral membrane
CC       protein. Endoplasmic reticulum membrane; Peripheral membrane
CC       protein.
CC   -!- PTM: S-nitrosylation by NOS2 (iNOS) activates enzyme activity. S-
CC       nitrosylation may take place on different Cys residues in addition
CC       to Cys-526 (By similarity). {ECO:0000250}.
CC   -!- MISCELLANEOUS: The conversion of arachidonate to prostaglandin H2
CC       is a 2 step reaction: a cyclooxygenase (COX) reaction which
CC       converts arachidonate to prostaglandin G2 (PGG2) and a peroxidase
CC       reaction in which PGG2 is reduced to prostaglandin H2 (PGH2). The
CC       cyclooxygenase reaction occurs in a hydrophobic channel in the
CC       core of the enzyme. The peroxidase reaction occurs at a heme-
CC       containing active site located near the protein surface. The
CC       nonsteroidal anti-inflammatory drugs (NSAIDs) binding site
CC       corresponds to the cyclooxygenase active site.
CC   -!- MISCELLANEOUS: Conversion of arachidonate to prostaglandin H2 is
CC       mediated by 2 different isozymes: the constitutive PTGS1 and the
CC       inducible PTGS2. PGHS1 is expressed constitutively and generally
CC       produces prostanoids acutely in response to hormonal stimuli to
CC       fine-tune physiological processes requiring instantaneous,
CC       continuous regulation (e.g. hemostasis). PGHS2 is inducible and
CC       typically produces prostanoids that mediate responses to
CC       physiological stresses such as infection and inflammation.
CC   -!- MISCELLANEOUS: PTGS1 and PTGS2 are the targets of nonsteroidal
CC       anti-inflammatory drugs (NSAIDs) including aspirin and ibuprofen.
CC       Aspirin is able to produce an irreversible inactivation of the
CC       enzyme through a serine acetylation. Inhibition of the PGHSs with
CC       NSAIDs acutely reduces inflammation, pain, and fever, and long-
CC       term use of these drugs reduces fatal thrombotic events, as well
CC       as the development of colon cancer and Alzheimer's disease. PTGS2
CC       is the principal isozyme responsible for production of
CC       inflammatory prostaglandins. New generation PTGSs inhibitors
CC       strive to be selective for PTGS2, to avoid side effects such as
CC       gastrointestinal complications and ulceration.
CC   -!- SIMILARITY: Belongs to the prostaglandin G/H synthase family.
CC       {ECO:0000305}.
DR   EMBL; AF047841; AAC05637.1; -; mRNA.
DR   ProteinModelPortal; O62725; -.
DR   SMR; O62725; -.
DR   PeroxiBase; 4136; MvPGHS02.
DR   HOVERGEN; HBG000366; -.
DR   UniPathway; UPA00662; -.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0031090; C:organelle membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0051213; F:dioxygenase activity; IEA:UniProtKB-KW.
DR   GO; GO:0020037; F:heme binding; ISS:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0004601; F:peroxidase activity; IEA:UniProtKB-KW.
DR   GO; GO:0004666; F:prostaglandin-endoperoxide synthase activity; ISS:UniProtKB.
DR   GO; GO:0019371; P:cyclooxygenase pathway; ISS:UniProtKB.
DR   GO; GO:0006954; P:inflammatory response; IEA:InterPro.
DR   GO; GO:0001516; P:prostaglandin biosynthetic process; ISS:UniProtKB.
DR   GO; GO:0008217; P:regulation of blood pressure; IEA:InterPro.
DR   GO; GO:0006979; P:response to oxidative stress; IEA:InterPro.
DR   Gene3D; 1.10.640.10; -; 1.
DR   InterPro; IPR029576; COX-2.
DR   InterPro; IPR000742; EGF-like_dom.
DR   InterPro; IPR019791; Haem_peroxidase_animal.
DR   InterPro; IPR010255; Haem_peroxidase_sf.
DR   InterPro; IPR037120; Haem_peroxidase_sf_animal.
DR   PANTHER; PTHR11903:SF8; PTHR11903:SF8; 1.
DR   Pfam; PF03098; An_peroxidase; 1.
DR   Pfam; PF00008; EGF; 1.
DR   PRINTS; PR00457; ANPEROXIDASE.
DR   SUPFAM; SSF48113; SSF48113; 1.
DR   PROSITE; PS50026; EGF_3; 1.
DR   PROSITE; PS50292; PEROXIDASE_3; 1.
PE   2: Evidence at transcript level;
KW   Dioxygenase; Disulfide bond; Endoplasmic reticulum;
KW   Fatty acid biosynthesis; Fatty acid metabolism; Glycoprotein; Heme;
KW   Iron; Lipid biosynthesis; Lipid metabolism; Membrane; Metal-binding;
KW   Microsome; Oxidoreductase; Peroxidase; Prostaglandin biosynthesis;
KW   Prostaglandin metabolism; S-nitrosylation; Signal.
FT   SIGNAL        1     17       {ECO:0000250}.
FT   CHAIN        18    604       Prostaglandin G/H synthase 2.
FT                                /FTId=PRO_0000023877.
FT   DOMAIN       18     55       EGF-like. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   ACT_SITE    193    193       Proton acceptor. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00298}.
FT   ACT_SITE    371    371       For cyclooxygenase activity.
FT                                {ECO:0000250|UniProtKB:Q05769}.
FT   METAL       374    374       Iron (heme axial ligand).
FT                                {ECO:0000255|PROSITE-ProRule:PRU00298}.
FT   BINDING     106    106       Substrate.
FT                                {ECO:0000250|UniProtKB:Q05769}.
FT   BINDING     341    341       Substrate.
FT                                {ECO:0000250|UniProtKB:Q05769}.
FT   SITE        516    516       Aspirin-acetylated serine.
FT                                {ECO:0000250|UniProtKB:P35354}.
FT   CARBOHYD     53     53       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    130    130       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    396    396       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    580    580       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID     21     32       {ECO:0000250|UniProtKB:Q05769}.
FT   DISULFID     22    145       {ECO:0000250|UniProtKB:Q05769}.
FT   DISULFID     26     42       {ECO:0000250|UniProtKB:Q05769}.
FT   DISULFID     44     54       {ECO:0000250|UniProtKB:Q05769}.
FT   DISULFID    555    561       {ECO:0000250|UniProtKB:Q05769}.
SQ   SEQUENCE   604 AA;  68950 MW;  E28D19F47CD926F8 CRC64;
     MLARAGLLCA SLSPPHAANP CCSNPCQNQG VCMSIGFDQY MCDCSRTGFY GENCSTPEFL
     TRVKLLLKPT PNTVHYILTH FKGVWNIVNK IPFLADVIMK YVRTSRSHCI EPPPTYNVHY
     AYKSWEAFSN LSYYTRALPP VADDCPTPMG VKGKKELPDS KEIVEKFLLR RKFIPDPQGT
     NMMFAFFAQH FTHQFFKTDH KRGPGFTKGL GHGVDLSHVY GETLDRQHKL RLFKDGKMKY
     QVIDGEVYPP TVKDTQVEMI YPPHVPEHLR FAVGQEVFGL VPGLMMYATI WLREHNRVCD
     VLKQEQGEWD DERLFRRSRL ILIGETIKIV IEDYVRHLSG YHFSLKFDPE LLFNQQFQYQ
     NRIAAEFNTL YHWHPLLPDT LQIDDQEYNF QQFVYNNSIL LEHGLTQFGE SFSRQIAGRV
     AGGRNVPAAV QQEQRASIDQ SRQMKYQSLN EYRKRFSVKP YASFEELTGE KEMAGELKAL
     YQDIDAMELY PALLVEKPRP DAIFGETMVE IGAPFSLKGL MGNPICSPDY WKPSHFGGEV
     GFKIINTASI QSLICNNVKG CPFTAFSVQD PQLTKTVTIN GSSSHSGLDD INPTVLLKER
     STEL
//
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